Targeting inflammation to prevent and treat cancers
Scientists show in preclinical model potentials from targeting TREM-1 gene
- Date : 31 Aug 2012
- Topic : Basic science
Researchers at the Georgia Health Sciences University Cancer Center have identified a gene that disrupts the inflammatory process implicated in liver cancer. The study, published in Cancer Research, a journal of the American Association for Cancer Research, could lead to drug therapies to target TREM-1. A study team, led by Dr Anatolij Horuzsko, an immunologist, has long suspected that chronic inflammation is a very powerful tool in the initiation of cancer, and also in the progression or metastasis of cancer.
Potentials of TREM-1-related cancer treatment
TREM-1's role in promoting inflammation is useful in cases such as battling viral or bacterial infections and in maintaining normal tissue function. But as Dr Horuzsko's team discovered, in abnormal conditions—such as liver damage due to alcohol abuse or other irritants—production of TREM-1 goes haywire. A chronic, low-level state of inflammation is produced as TREM-1 leads to the development of other inflammatory agents, which causes more damage, increases cell production and creates mutated cells. These mutated cells then reproduce—planting the seeds that can lead to cancer.
During the 14-month study, Dr Horuzsko and his team used mouse studies to gather data on the effect of TREM-1 in the liver cells and identify potential sources for therapies. Because a mouse's life span is about three years, the length of the study mimicked a similar 20- to 30-year cancer progression of liver cancer in humans.
Two sets of mice—one with the TREM-1 gene removed—were exposed to the cancer-causing agent diethylnitrosamine, or DEN, which is present in tobacco smoke, chemicals and other products. Within just 48 hours of DEN injection, the control mice were already showing signs of liver cell injury and death and high levels of TREM-1 expression in the liver's Kupffer cells. These specialised liver cells normally destroy bacteria and worn-out red blood cells. Eight months later, these mice also showed massive liver tumours.
But the mice with the gene removed remained healthy, showing very few changes—and very small, if any, tumours after eight months. The only difference between the two groups was the appearance of TREM-1 in the Kupffer cells.
Dr Horuzko's team hopes the findings—and their potential in TREM-1-related cancer treatment—will be applicable to other cancers as well. TREM-1 could be a target for any inflammation-associated cancer, and in the future, the researchers could use a drug to target TREM-1. They are already working in this direction.
Dr Horuzsko's team also identified another potential target for drug therapy during the study—HMGB1. HMGB1 is an activating ligand, or agent, that stimulates Kupffer cells to produce the TREM-1 protein and start the inflammatory process.
The Cancer and Inflammation Program at the USA National Cancer Institute also provided work on this study, which was funded by National Institutes of Health grants.
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